- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03811652
A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors
A Phase 1/1b Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI7247 in Patients With Advanced or Metastatic Disease in Selected Solid Tumors
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Ontario
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Toronto, Ontario, Canada, M5G 2M9
- Research Site
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North Carolina
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Huntersville, North Carolina, United States, 28078
- Research Site
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Tennessee
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Nashville, Tennessee, United States, 37203
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Confirmed diagnosis of advanced or metastatic select solid tumors and either progression on or documented intolerance to standard therapies
- Age ≥ 18 years at the time of screening.
- Written informed consent and any locally required authorization
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- At least 1 measurable target lesion by CT or MRI per RECIST Version 1.1 (excluding mCRPC)
- Adequate Liver Function: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × ULN (upper limit normal), Albumin > 3 g/dL, and serum total bilirubin (TBL) ≤ 1.5 × ULN; (unless bilirubin rise is due to Gilbert's syndrome, hepatic metastases or of non-hepatic origin, in which case TBL ≤ 3 × ULN is allowed)
- Creatinine Clearance (CrCL) ≥ 40 mL/min
- Adequate Hematopoesis: Absolute Neutrophil Count (ANC) ≥ 1,500/μL, Platelets ≥ 100,000/μL, and Hgb ≥ 9 g/dL unassisted by transfusion or growth factor within 14 days of screening
- Provision of archival or fresh tumor tissue at screening
- Female patients of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception, and must agree to continue using such precautions for 90 days after the last dose of investigational product.
- Nonsterilized male patients who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from 7 days post-screening and for 90 days after receipt of the last dose of investigational product.
Exclusion Criteria:
- Active central nervous system (CNS) metastases, unless adequately treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) and prednisolone 10 mg or less for more than 2 weeks prior to enrollment. For SCLC, a brain MRI scan that was conducted ≤ 28 days from Day 1 is required.
- Residual toxicity from prior anticancer therapy not resolved to NCI CTCAE v4.03 Grade 1, with the exception of alopecia/vitiligo at the time of first dose of investigational product. For patients previously receiving immunotherapy, toxicities that are unlikely to recover to Grade 1.
- Royal Marsden Hospital (RMH) prognostic score 2 and 3 at baseline.
- Treatment with anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 21 days, or prior palliative radiotherapy within 2 weeks of the first dose of investigational product.
5 Prior treatment with other Pyrrolobenzodiazepine-Antibody Drug Conjugates.
6 History of previous malignancies (except for locally curable cancers) unless a complete remission was achieved at least 3 years prior to study entry AND no additional therapy is required during the study period (except adjuvant hormonal therapy and bisphosphonate).
7. Failure to recover from major surgery or significant traumatic injury within 21 days of first dose of study treatment.
8 History of hepatic sinusoidal obstruction syndrome, also called veno-occlusive disease 9. History of capillary leak syndrome. 10 Blood transfusion within 14 days of study entry except when needed for disease related anemia.
11. New York Heart Association classes III-IV congestive heart failure or serious cardiac arrhythmia requiring treatment, history of myocardial infarction, unstable angina, vascular stent, or coronary artery bypass graft within 6 months of the first dose of investigational product. 12. Active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infections at the time of screening.
13. Current severe active systemic disease including active concurrent malignancy 14. Pregnancy and/or breastfeeding at time of screening 15. Concurrent enrollment in anther clinical study involving an investigational treatment that is not an extension of another MedImmune study with the same investigational product.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: NSCLC-Sq/HNSCC
Patients with advanced or metastatic NSCLC-Sq or HNSCC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior standard of care regimen (platinum-based for HNSCC).
PDL-1 positive patients should have received previous PD-1 or PD-L1 inhibitor where available.
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Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
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Experimental: Small Cell Lung Cancer
Patients with advanced SCLC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior standard of care regimen.
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Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
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Experimental: Colorectal Cancer
Patients with metastatic adenocarcinoma of the colon or rectum who have received and have progressed, or have documented intolerance, on prior thymidylate synthase inhibitor (eg, 5-fluorouracil (5-FU), capecitabine, raltitrexed, tegafur-uracil (UFT), irinotecan, and oxaliplatin for metastatic disease.
If patients progress within 6 months of their last dose of adjuvant therapy this should be considered as a line of therapy in the metastatic setting.
Patients with known RAS wildtype tumors must have received and progressed, or have documented intolerance, on anti-EGFR antibody.
Patients with microsatellite instability-high or deficient mismatch repair tumors, must have received and progressed, or have documented intolerance on a PD-1 inhibitor, or PD-1 inhibitor plus cytotoxic T-lymphocyte antigen-4 inhibitor treatment where available.
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Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
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Experimental: Pancreatic Ductal Adenocarcinoma
Patients with unresectable, locally advanced or metastatic PDAC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior line of treatment.
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Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
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Experimental: Metastatic Castration-Resistant Prostate Cancer
Patients with mCRPC who have received prior treatment with abiraterone or enzalutamide, with or without a prior taxane-based chemotherapy in the mCRPC setting.
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Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
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Experimental: Other advanced/metastatic target expressing solid tumors
Patients with advanced or metastatic solid tumors not defined by other treatment arms who have positive expression of the protein target and have exhausted all approved therapies
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Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Occurrence of Adverse Events
Time Frame: From time of informed consent through 90 days post end of treatment
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To assess the occurrence of adverse events
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From time of informed consent through 90 days post end of treatment
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Occurrence of Serious Adverse Events
Time Frame: From time of informed consent through 90 days post end of treatment
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To assess the occurrence of serious adverse events
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From time of informed consent through 90 days post end of treatment
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Occurrence of Dose Limiting Toxicities
Time Frame: During the evaluation period of 21 days post first dose
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To assess the occurrence of toxicities and abnormal laboratory results that may limit further dose administration
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During the evaluation period of 21 days post first dose
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Number of patients with changes in laboratory parameters from baseline
Time Frame: From time of informed consent through 90 days post end of treatment
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To assess serum chemistry, hematology, urinalysis and coagulation parameters
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From time of informed consent through 90 days post end of treatment
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Number of patients with changes in vital signs parameters from baseline
Time Frame: from time of informed consent through 21 days post last dose
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to assess changes in vital signs
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from time of informed consent through 21 days post last dose
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Number of patients with changes in electrocardiogram results from baseline
Time Frame: from time of informed consent through 21 days post last dose
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to assess changes in ECG
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from time of informed consent through 21 days post last dose
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Percentage of patients with changes in laboratory parameters from baseline
Time Frame: from time of informed consent through 90 days post end of treatment
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to assess changes in serum chemistry, hematology, urinalysis, and coagulation parameters
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from time of informed consent through 90 days post end of treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MEDI7247 maximum observed concentration (Cmax)
Time Frame: From first dose through 90 days post end of treatment
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To characterize MEDI7247 single agent Pharmacokinetics
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From first dose through 90 days post end of treatment
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MEDI7247 terminal half life (t1/2)
Time Frame: From first dose through 90 days post end of treatment
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To characterize single agent MEDI7247 pharmacokinetics
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From first dose through 90 days post end of treatment
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MEDI7247 area under the concentration/time curve (AUC)
Time Frame: from first dose through 90 days post end of treatment
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To characterize single agent MEDI7247 pharmacokinetics
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from first dose through 90 days post end of treatment
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MEDI7247 clearance
Time Frame: from first dose through 90 days post end of treatment
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to characterize the single agent MEDI7247 pharmacokinetics
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from first dose through 90 days post end of treatment
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Number of subjects who develop anti-drug antibodies
Time Frame: first dose through 90 days post end of treatment
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To characterize MEDI7247 immunogenicity
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first dose through 90 days post end of treatment
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Best Overall Response
Time Frame: From time of informed consent and up to 90 days post end of treatment
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To assess antitumor activity of MEDI7247
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From time of informed consent and up to 90 days post end of treatment
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Objective Response Rate (ORR)
Time Frame: From time of informed consent and up to 2 years after last subject in
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To assess antitumor activity of MEDI7247
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From time of informed consent and up to 2 years after last subject in
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Time to Response (TTR)
Time Frame: From time of informed consent and up to 90 days post end of treatment
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To assess antitumor activity of MEDI7247
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From time of informed consent and up to 90 days post end of treatment
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Duration of Response (DoR)
Time Frame: From time of informed consent and up to 2 years after last subject in
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To assess antitumor activity of MEDI7247
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From time of informed consent and up to 2 years after last subject in
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Progression Free Survival (PFS)
Time Frame: From time of informed consent and up to 2 years after last subject in
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To assess the antitumor activity of MEDI7247
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From time of informed consent and up to 2 years after last subject in
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Disease Control (DC)
Time Frame: From time of informed consent and up to 2 years after last subject in
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To assess antitumor activity of MEDI7247
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From time of informed consent and up to 2 years after last subject in
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Overall Survival (OS)
Time Frame: From time of informed consent and up to 2 years after last subject in
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To assess antitumor activity of MEDI7247
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From time of informed consent and up to 2 years after last subject in
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Urogenital Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Genital Neoplasms, Male
- Prostatic Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Head and Neck Neoplasms
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Carcinoma, Squamous Cell
- Prostatic Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Colorectal Neoplasms
- Adenocarcinoma
- Small Cell Lung Carcinoma
- Squamous Cell Carcinoma of Head and Neck
Other Study ID Numbers
- D8540C00002
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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